Objectives To evaluate the changes in inflammatory cytokines, such as interleukin (IL)-8 and IL-6, in the cerebrospinal fluid (CSF) and serum, and to identify any correlations with the neurological outcomes in patients resuscitated from cardiopulmonary arrest (CPA). Materials and methods This study was designed as a prospective clinical trial. Thirteen patients, who were resuscitated from out-of-hospital CPA and survived for more than 48 h, were enrolled in this study. Arterial blood was taken from the patients at 48 h after the return of spontaneous circulation (ROSC) and CSF was taken by lumbar puncture at the same time. Results In the CSF, the median levels of IL-8 and IL-6 in the patients resuscitated from CPA were significantly higher than those in the control subjects (1311 pg/ml vs 82 pg/ml, P < 0.001; 2040 pg/ml vs 1 pg/ml, P < 0.001, respectively). The Glasgow Outcome Scale (GOS) score evaluated at 6 months after the ROSC correlated significantly with the levels of IL-8 and IL-6. The cutoff values and sensitivity values with 100% specificity for the prediction of an unfavorable neurological outcome were 1423 pg/ml and 86% for IL-8, and 2708 pg/ml and 86% for IL-6, respectively. Conclusion We demonstrated the cutoff values of IL-8 and IL-6 in the CSF to predict the neurological outcome in the patients resuscitated from CPA. The excessive inflammatory cytokine reactions in the brain might therefore be related to the poor neurological outcome in patients with post-resuscitation encephalopathy.